The technique of embryo transfer which involves inseminating eggs of female livestock having excellent genetic characters with sperms of male livestock also having excellent genetic characters, and culturing the fertilized eggs in vitro, followed by their transfer to the uterus of another female livestock (recipient) has been widely practiced as a technique of efficiently yielding superior livestock or laboratory animals. Examples of such a widely practiced technique include: in vivo fertilized egg transfer which involves transferring fertilized eggs harvested from a donor (source animal of the fertilized eggs) to a recipient (animal which receives the fertilized eggs) synchronized to induce pseudopregnancy by hormone treatment or the like, and allowing the resulting pregnant animal to give birth; and in vitro fertilized egg transfer which employs fertilized eggs in a state transferable in utero produced by isolating immature ova from the ovary of livestock after failure-no-failure confirmation of fresh, etc., obtained in a slaughterhouse, followed by the in vitro maturation, fertilization, and developmental culture of the ova.
As for humans, Dr. Edwards and Dr. Steptoe reported, in 1978, success in in vitro fertilization (IVF)-embryo transfer (ET) method which involves fertilizing ova with sperms in an in vitro culture solution, and transferring the in vitro cultured embryos in utero (see, for example, non-patent document 1). Furthermore, HTF medium (human tubal fluid medium) having composition similar to the electrolytic composition of a human oviductal fluid serving as a fertilization site has been developed as a medium for human in vitro fertilization (see, for example, non-patent document 2). This has made the beginning of studies on a medium for in vitro fertilization instead of a versatile medium previously used such as Ham's F-10 medium.
As such media for in vitro fertilization, there have been proposed, for example, a medium composition for artificial insemination containing sericin, wherein embryos harvested by in vivo artificial insemination, or embryos yielded by in vitro fertilization can be cultured (see, for example, patent document 1), a medium composition for artificial insemination containing xanthophyll (see, for example, patent document 2), a medium for the in vitro culture of pig embryos, comprising pyruvic acid or lactic acid or a salt thereof, and taurine or a precursor thereof as essential components (see, for example, patent document 3), a method for improving a development rate of fertilized mammalian eggs, comprising adding a vascular endothelial growth factor to a development medium for fertilized mammalian eggs, and coculturing the eggs with feeder cells so that the normal development rate of the fertilized eggs is enhanced (see, for example, patent document 4), an amino acid-containing medium composition for in vitro fertilization substantially free from L-glutamine or a derivative thereof capable of forming L-glutamine by hydrolysis (see, for example, patent document 5), a medium composition for in vitro fertilization usable in mammalian ovum or early embryo culture or sperm preparation or culture, containing 21 types of amino acids contained in follicular fluids, or derivatives thereof capable of forming such amino acids by hydrolysis, in free forms or in forms of pharmacologically acceptable salts thereof (see, for example, patent document 6), a serum-free medium for the in vitro culture of fertilized bovine eggs, consisting of low-glucose concentration TCM199 medium containing lactic acid or a soluble salt thereof, pyruvic acid or a soluble salt thereof, a basic fibroblast growth factor, and tumor growth factor-β1 (see, for example, patent document 7), and a method for improving a conception rate, comprising allowing magnetic force to act on sperms of a male, ova of a female, or fertilized eggs obtained therefrom (see, for example, patent document 8).
Intracytoplasmic sperm injection (ICSI) which involves aspirating sperms into a pipette for sperm injection and injecting the sperms into the ooplasm has been further developed as one form of the IVF method. This method produces fertilized eggs at high yields even from one sperm and is therefore also effective for infertility caused by male infertility including severe oligospermia. Although the in vitro culture of fertilized eggs has become a general approach as mentioned above, it is known that the development of the cultured fertilized eggs falls short of the blastocyst stage and is arrested before the morula stage at high rates. As pointed out, this might be because some factor causes the arrest of early development, though the mechanism has yet been unknown. In the case of, for example, humans, the pregnancy rate of in vitro fertilization is approximately 20 to 25% of the total in vitro fertilization number, and only 5 to 15% thereof reportedly arrives at birth. It has also been reported as to cattle that in the in vitro culture of fertilized eggs, the development thereof is often arrested at the 8-cell stage to the 16-cell stage (see, for example, non-patent document 3).
Meanwhile, 5-aminolevulinic acid (5-ALA) is known as an intermediate of the tetrapyrrole biosynthesis pathway widely found in animals, plants, and fungi, and is generally biosynthesized from succinyl CoA and glycine by 5-aminolevulinic acid synthase. Photodynamic therapy using 5-ALA (ALA-PDT) has also been developed and has received attention as a treatment method that is low invasive and maintains QOL. For example, diagnostic or therapeutic agents for tumors using ALA or the like have been reported. In addition, 5-ALA is also known to be useful as a prophylactic or ameliorating agent or a therapeutic agent for adult-onset diseases, cancers, and male infertility (see, for example, patent documents 9 to 11).